Lentigines are common pigmentary by hyperpigmentation secondary to an increased number of melanocytes. Multiple Lentigines Syndrome (MLS) is an inherited disease that results in generalized lentigines. Other manifestations of MLS may include developmental, auditory, and cardiovascular abnormalities. MLS is associated with skin findings phenotypically similar to those in the LEOPARD syndrome (MIM 151100). The clinical manifestations, which encompass the LEOPARD syndrome, include: Lentigines, ECG abnormalities, Ocular hypertelorism/Obstructive cardiomyopathy, Pulmonary valve stenosis, Abnormalities of genitalia in males, Retardation of growth, and Deafness. MLS also belongs to a group of genetic syndromes, the lentiginoses disorders. In these disorders, cutaneous abnormalities, such as lentigines, and non-cutaneous abnormalities, such as familial neoplasias and diverse developmental defects, manifest on a shared but variable basis. No clinical research studies on MLS or LEOPARD syndrome have been conducted. Neither the full extent of the clinical disease nor the basic cause of the disease is known. This proposal seeks support to train a young investigator in patient-oriented research. The proposal is a three-phase study of Multiple Lentigines Syndrome (MLS): genomics, clinical investigation, and diadactic study. If the proposal is funded, then the investigator: (i) will pursue a molecular basis for the Multiple Lentigines Syndrome (MLS) and will investigate whether a molecular link exists between MLS and LEOPARD Syndrome; (ii) will investigate whether a relationship exists between MLS and common pigmentation anomalies and, if so, whether this research can be used as the basis for new diagnostic and therapeutic methodologies, and (iii) will pursue extensive coursework in research and medical ethics; and will obtain experience with health sciences research, human genetics, molecular and cellular biological techniques, biostatistics, and clinical center regulations. Theresa Pacheco, M.D. is an Assistant Professor of Dermatology and is committed to a career in clinical research with an focus on molecular markers of disease (pigmentation anomalies) and patient-oriented research topics.